Biomarkers may predict who will respond to breast cancer prevention therapy

Single nucleotide polymorphisms (SNPs) in or near the genes ZNF423 and CTSO were associated with breast cancer risk among women who underwent prevention therapy with tamoxifen and raloxifene, according to recently published data.

This study found that women who have the favorable variations on these two SNPs are more likely to respond to prevention therapy. Women with the unfavorable variations of these SNPs may not benefit from prevention therapy, and their risk of developing breast cancer is five-fold higher. The study was published in Cancer Discovery (2013; doi:10.1158/2159-8290.CD-13-0038).

"The recent guidelines by the US Preventive Services Task Force emphasize that selective estrogen receptor modulator (SERM) therapy with tamoxifen and raloxifene can lower a woman's risk for developing breast cancer. But about 50 women have to be exposed to the treatment and side effects to prevent a single case of breast cancer," said lead author James N. Ingle, MD, of the Mayo Clinic in Rochester, Minnesota.

"Our findings are important, because for the first time, we discovered genetic factors that could be used to select women who should be offered the drugs for prevention. Also of substantial importance is that we have discovered new information on how tamoxifen and raloxifene work to prevent breast cancer."

Ingle and his research team conducted a genome-wide association study involving 592 patients who developed breast cancer while on SERM therapy and 1,171 matched controls. They selected participants from the 33,000 women enrolled in the NSABP P-1 and P-2 breast cancer prevention trials.

He and his colleagues analyzed participants' DNA using the Illumina Human610-Quad BeadChip to identify variations in their genetic makeup. They identified two SNPs that were most relevant to breast cancer risk, one in the gene ZNF423, and the other near the gene CTSO.

"Our discovery is a major step toward truly individualized prevention of breast cancer. Findings from our study provide clear direction as to which women are likely and which are unlikely to benefit from tamoxifen or raloxifene," said Ingle. "The best chance we have of decreasing the burden of breast cancer is to prevent it in the first place. Our findings provide the basis for a reinvigoration of research efforts in breast cancer prevention."